RAB27A (RAB27A, Member RAS Oncogene Family)

MicroRNA-29c-3p was identified as a cargo of leptin-stimulated BAT-derived EVs and appears to play a key role in mitigating cardiac fibrosis after ischemia-reperfusion injury in leptin-treated animals. Activation of LepR in the brain protects the heart after ischemia-reperfusion injury via sympathetic-mediated BAT-derived EVs enriched with microRNA-29c-3p.

These results suggest that LOWEO may exert skin-whitening and anti-hyperpigmentation effects by suppressing melanin production and interfering with melanosome transport in B16BL6 cells. Therefore, LOWEO should be considered a promising developmental starting point for natural agents that alleviate and/or prevent skin hyperpigmentation.

We show that knockdown of the GTPase Rab27a abrogates IR-induced EV secretion and inhibits the enrichment of key DAMPs in EVs. By examining the integration of cellular damage and senescence with the release of inflammatory signals, this study elucidates a potentially critical role for EV-associated proteins in the radiation response.

Cells were treated with 20 μM hydrogen peroxide (H2O2) for 4 days, and physicochemical properties of Exos were analyzed using dynamic light scattering (DLS), scanning electron microscope (SEM), and western blotting. The expression of genes such as ALIX, CD63, TSG101, Rab27a, and Rab27b, along with aging factor senescence-associated

In addition, conditioned medium from HaCaT cells irradiated with UVA (CM-UVA) in the presence of CPEO reduced melanin synthesis and tyrosinase activity in B16BL6 cells (e.g., at CM-UVA with 100 μg/mL CPEO, melanin synthesis: 100.92 ± 0.99% vs. 134.44 ± 0.97% with CM-UVA; tyrosinase activity: 101.02 ± 1.81% vs. 133.77 ± 1.88% with CM-UVA). These findings suggest that CPEO inhibits melanin production (probably through the regulation of MAPKs) and transport-related activities in B16BL6 cells, and that CPEO may serve as a potential natural anti-hyperpigmentation or skin whitening.

Indeed, we find that SYTL5 interacts with proteins involved in vesicle-mediated transport and cellular response to stress and that its depletion compromises mitochondrial respiration and increases glucose uptake. Intriguingly, SYTL5 expression is significantly reduced in tumours of the adrenal gland and correlates positively with survival for patients with adrenocortical carcinoma.

Furthermore, we verified that exosomal IGF2 aggravated HCC migration and invasion via activating Ras/Raf/Erk signaling in recipient cells. Collectively, our data demonstrated that exosomes from FSS-stimulated HCC cells promote recipient cell migration through IGF2-Ras/Raf/Erk signaling, which might serve as potential targets for both cancer treatment and cancer prevention.

A specific EV subpopulation enriched in CD147 and LAMB1-referred to as Excretion EVs-carried H3.2 (H3C14) but did not induce GCB resistance in recipient cells, suggesting their primary role in eliminating proteins associated with tumour progression and drug resistance. These findings highlight the role of EV-mediated H3C14 excretion in regulating GCB resistance and suggest potential therapeutic strategies targeting EV pathways to overcome drug resistance in bladder cancer.

These results emphasize the challenges of interfering with EV secretion, as several parallel pathways, such as direct membrane budding, can compensate. Further studies are needed to develop models for studying the role of EVs in vivo.

This study provides the first evidence of a regulatory relationship between PAX3 and NF-κB, wherein NF-κB directly binds to the enhancer regions of Rab27a and Mlph to modulate melanosome transport. These findings offer novel insights into the transcriptional control of melanogenesis and its potential implications for melanoma research.

P1/2, N=10, Active, not recruiting, St. Jude Children's Research Hospital | Trial primary completion date: Aug 2025 --> Nov 2025

Importantly, PD-L1 sorting relies on a ternary complex composed of Munc13-4, PD-L1 and HRS, which is regulated by interferon gamma (IFNγ) signaling. A designed peptide that disrupts Munc13-4-PD-L1 interaction impedes PD-L1 sorting, enhances antitumor immunity, and suppresses tumor growth, highlighting the therapeutic potential of targeting this pathway.